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Researchers in the US have identified the gene mutation that may be the cause of a deadly form of childhood cancer, opening the way to genetic tests for high-risk families.

The same wayward gene has been previously linked to lymphoma and lung cancer in adults, so afflicted children could benefit from experimental drugs designed to suppress its activity, according to the study which appears in Nature.

"This very important discovery not only helps us understand the genetic roots of this terrible disease, but also has led to dramatically new ideas for curative therapy," says lead researcher Dr John Maris, head of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia.

Neuroblastoma attacks the nervous system. While fairly rare, it accounts for 7% of all childhood cancers, and 15% of non-adult cancer deaths.

Puzzling

The disease has long puzzled scientists because of its highly variable outcomes: some forms strike infants but then recede without treatment, while other variants, especially in older children, can be relentlessly aggressive.

"This discovery enables us to offer the first genetic tests to families affected by the inherited form of this disease," says study lead author Dr Yael Mosse.

"Because there are already drugs in development that target the same gene in adult cancers, we can soon begin testing those drugs in children with neuroblastoma," she says.

An international team led by Maris scanned genomes - the DNA library unique to every individual - within 10 families beset by the disease.

The first broad scan narrowed the hunt to one particular chromosome, number 2. Another round of sequencing revealed that eight of the ten families had the same telltale variant in one spot, the anaplastic lymphoma kinase (ALK) gene.

Simpler tests

The findings will make it possible to use simple ultrasound or urine tests to monitor children with this mutation so that any signs of the cancer can be tackled at an early stage.

After pinpointing the source of familial neuroblastoma, the researchers asked whether the ALK mutations played a role in the so-called sporadic, or non-inherited, forms of the disease.

They found that it occurred in 12% of 194 tumour samples taken from a particularly aggressive, high-risk variant.

Earlier research on lymphoma and lung cancer in adults had shown that ALK acts through a process called translocation in which DNA is exchanged across chromosomes to produce a fusion gene.

According to the study, it is the first to identify a childhood cancer caused by mutations in a cancer-causing gene.

Since the mutations discovered trigger an "on" signal for neuroblastoma cells, the abnormality is a prime target for therapies that block the ALK protein.

Several pharmaceutical companies are developing ALK inhibitors, and one is already in early-phase adult clinical trials against lung cancer and lymphoma.

"It's an advantage to be able to start with agents that have already been shown to be safe in adults," says Mosse.